Identification of the Ca2+ entry pathway involved in deoxygenation-induced phosphatidylserine exposure in red blood cells from patients with sickle cell disease

被引:0
作者
U. M. Cytlak
A. Hannemann
D. C. Rees
J. S. Gibson
机构
[1] Department of Veterinary Medicine,Department of Paediatric Haematology, King’s College Hospital NHS Foundation Trust
[2] King’s College London School of Medicine,undefined
来源
Pflügers Archiv - European Journal of Physiology | 2013年 / 465卷
关键词
Sickle cell disease; Red blood cell; Phosphatidylserine; Deoxygenation; Calcium; Cation channel;
D O I
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中图分类号
学科分类号
摘要
Phosphatidylserine (PS) exposure in red blood cells (RBCs) from sickle cell disease (SCD) patients is increased compared to levels in normal individuals and may participate in the anaemic and ischaemic complications of SCD. Exposure is increased by deoxygenation and occurs with elevation of intracellular Ca2+ to low micromolar levels. The Ca2+ entry step has not been defined but a role for the deoxygenation-induced pathway, Psickle, is postulated. Partial Psickle inhibitors 4-acetamido-4′-isothiocyanostilbene-2,2′-disulphonic acid (SITS), 4,4′-dithiocyano-2,2′-stilbene-disulphonic acid (DIDS) and dipyridamole inhibited deoxygenation-induced PS exposure (DIDS IC50, 118 nM). Inhibitors and activators of other pathways (including these stimulated by depolarisation, benzodiazepines, glutamate and stretch) were without effect. Zn2+ and Gd3+ stimulated PS exposure to high levels. In the case of Zn2+, this effect was independent of oxygen (and hence HbS polymerisation and RBC sickling) but required extracellular Ca2+. The effect was completely abolished when Zn2+ (100 μM) was added to RBCs suspended in autologous plasma, implying a requirement of high levels of free Zn2+.
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页码:1651 / 1660
页数:9
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